This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a TNF-Blocker. (NCT00424502), a na phase 4 study. The primary outcome is Disease Activity Score Based on 28-Joint Count (DAS28).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00424502 |
| Phase | Phase 4 |
| Condition | Rheumatoid Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 20 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
People with active rheumatoid arthritis whose current treatment with one or more TNF blockers had produced an inadequate response. The primary endpoint population was all enrolled participants who received at least one dose of study treatment.
Intervention
Rituximab, identified as MabThera, given by infusion at 1 g on Day 1 and Day 15, with participants continuing basic methotrexate therapy of 10–25 mg per week.
Comparator
There was no separate comparator group. The study was single-group, and the registry lists allocation as NA.
Primary question
How did mean Disease Activity Score based on 28-joint count (DAS28) appear at Day 0 and Week 24 among treated participants? Numerical DAS28 results are not reported in the registry record.
This is a descriptive question about outcomes in a treated group, not a randomized comparison of rituximab with another treatment or with no treatment. The record identifies a population with active rheumatoid arthritis and an inadequate response to previous TNF inhibition, then specifies DAS28 as the primary measure. DAS28 combines joint counts, an inflammation measure, and a participant assessment of disease activity.
Because no comparator group is recorded, the study cannot directly estimate how outcomes would have differed under another treatment strategy. A difference between measurements over time, if reported, would describe the observed course in this group; it would not by itself separate treatment effects from changes that might have occurred for other reasons. In this registry record, even the numerical values needed to describe that course are absent. The primary question can therefore be identified, but the size and precision of any observed DAS28 result cannot be assessed from the record.
3. Trial Design
The registry identifies this as a completed Phase 4 study sponsored by Hoffmann-La Roche. It began in 2007-01 and had a primary completion date of 2009-10. The recorded enrollment was 20 participants. The study is described as open-label, with no masking, and as a single-group study. Allocation is listed as NA, consistent with the absence of a separate allocated comparison group in the record.
The study summary describes participants with active rheumatoid arthritis whose current treatment with one or more TNF blockers had produced an inadequate response. Participants were to receive rituximab, identified as MabThera, by 1 g infusion on Day 1 and Day 15, while continuing basic methotrexate therapy at 10–25 mg per week. The anticipated time on study treatment was 3–12 months. The summary also describes a target sample size of fewer than 100 individuals; this is distinct from the recorded enrollment of 20.
The primary outcome was DAS28, assessed at Day 0 and Week 24 and expressed as a mean with standard deviation. The specified primary population was all enrolled participants who received at least one dose of study treatment. Secondary outcome measures listed in the record include HAQ-DI, anti-CCP, VEGF, ESR, and CRP. The record lists six outcome measures and four analyses, but it does not provide enough detail to determine how each analysis relates to each measure.
A single-group, open-label design can describe outcomes and safety observations among participants treated in the study. It does not provide a like-for-like control comparison, and the record does not report randomization or masking. Numerical primary outcome results and a detailed statistical analysis plan are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Rituximab 1000 Milligrams (mg) |
|---|---|
| STARTED | 20 |
| COMPLETED | 20 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: All enrolled participants who received at least one dose of study treatment.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: All enrolled participants
| Characteristic | Unit | Rituximab 1000 mg |
|---|---|---|
| Participants analysed | 20 | |
| Age, Continuous | years | 48.70 (SD 12.88) |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Disease Activity Score Based on 28-Joint Count (DAS28), measured over Day 0 and Week 24.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
DAS28 is a continuous measure of rheumatoid arthritis disease activity based on a 28-joint count. As described in the record, it includes swollen joint count, tender joint count, erythrocyte sedimentation rate in millimeters per hour, and a participant-rated global assessment of arthritis activity. The transformed score ranges from 0 to 10. Higher scores indicate greater affectation due to disease activity.
The registry describes a score equal to or less than 3.2 as low disease activity and a score greater than 3.2 to 5.1 as moderate to high disease activity. These thresholds provide clinical context for interpreting a measured score, but they do not replace examination of the actual results, their variability, or the analysis used. The record specifies the mean and standard deviation as the summary measures and Day 0 and Week 24 as the assessment times.
General: A continuous endpoint retains information about the magnitude of a measurement, rather than reducing each participant’s result to a yes-or-no category. A mean describes the group’s average score, while a standard deviation describes the spread of individual scores around that average. Considering both can help distinguish a group average from the variation among participants.
The registry record does not report the numerical DAS28 means or standard deviations at either assessment time, nor does it state a numerical change estimate. It is therefore not possible to describe the observed endpoint level, its variation, or the precision of a comparison between the recorded time points from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes the study question and its design, but it does not report numerical results for the primary DAS28 endpoint. Although Day 0 and Week 24 are named as assessment times and the outcome is defined as a mean with standard deviation, the corresponding values are not reported in the registry record. Consequently, the magnitude and direction of the observed DAS28 results cannot be described from this record, and their precision cannot be assessed.
The design also limits the type of interpretation that would be possible even if a group’s results over time were available. This was a single-group, open-label study, not a randomized comparison. A change in the group average between assessment times could describe what occurred among participants in the study, but it would not by itself establish what would have happened to the same participants under a different treatment strategy. Without a comparator group, differences attributable to treatment cannot be separated from other possible influences on outcomes.
General: Statistical precision concerns how much uncertainty surrounds an estimate. A confidence interval, when reported, gives a range of values compatible with the data and the method used to calculate it. A narrower interval generally indicates greater precision than a wider interval, but neither width nor statistical significance alone determines clinical importance. No confidence interval for the primary outcome is reported in the registry record.
The listed enrollment was 20, but enrollment alone does not reveal the number contributing to a particular endpoint at each assessment. The record defines the primary population as all enrolled participants who received at least one dose, but does not report endpoint-specific participant counts or missing-data handling. It also does not report a p-value for DAS28. Thus, no claim about statistical significance, precision, or the completeness of the endpoint analysis can be made from the registry entry.
The record lists other outcome measures, including HAQ-DI, anti-CCP, VEGF, ESR, and CRP. Their presence indicates that additional measures were tracked, but their numerical results and the relationships among the analyses are not reported. The record does not describe whether any multiplicity adjustment was used. Results for these other measures therefore cannot be used to qualify or corroborate the primary endpoint.
The observed safety counts are also descriptive. The record reports no participants affected by a serious adverse event among 20 at risk, and nine participants affected by other adverse events among 20 at risk. These counts do not establish whether an event was caused by treatment, and the registry record does not report deaths. They should be read as recorded counts in this study, not as a controlled estimate of comparative safety.
9. Statistical Methods Explained
Interpreting the study requires separating the statistical question from the design and from the information actually reported. The central endpoint is continuous, the study has one group, and the registry record gives assessment times but no numerical endpoint results. Statistical concepts can explain what the specified summaries would mean, but they cannot supply missing results.
What does a mean and standard deviation describe?
General: A mean is the arithmetic average of participant measurements in the analysis being described. For DAS28, it would summarize the group’s average score at a specified assessment time, assuming the analysis used the stated endpoint and population. A mean does not show whether all participants had similar scores or whether the average was influenced by a range of individual values.
General: A standard deviation describes the spread of observations around the mean. A larger standard deviation indicates more variation among the observed measurements, while a smaller one indicates less variation. It is not the same as the uncertainty in the mean. The standard deviation concerns participant-level variability; a confidence interval for the mean concerns the precision of the estimated average and depends on the data and analysis method.
The registry identifies the primary summary as mean and standard deviation, but does not report their values for Day 0 or Week 24. Without those values, neither the average score nor the observed variability can be evaluated. The record also does not state whether the principal numerical contrast was a change, a Week 24 value, or another summary of the two assessment times.
What does the single-group design allow?
General: A single-group study can describe measurements and events among participants receiving the study treatment. When outcomes are recorded at more than one time, a within-group comparison can describe how observed measurements differ across those times. Such a comparison is not the same as a randomized treatment contrast. A control group can help account for changes that might also occur without the treatment under study, whereas this record lists no comparator.
The open-label design means masking is recorded as none. General: Knowledge of treatment assignment can affect participant-reported measures, clinical assessments, care decisions, or reporting of events. That is a design consideration, not proof that any particular measurement was biased. The record does not describe additional procedures intended to address such concerns.
How should the endpoint thresholds be used?
The DAS28 description gives the scale range and defines score categories: equal to or less than 3.2 is low disease activity, and greater than 3.2 to 5.1 is moderate to high disease activity. Higher scores indicate greater affectation due to disease activity. These definitions help interpret a score’s scale, but they do not reveal where participants’ scores fell. Since the numerical endpoint results are not reported in the registry record, the categories cannot be applied to characterize the study group’s observed results.
General: A continuous score and a category derived from that score answer different questions. The score retains distinctions across its scale; a category groups scores according to a threshold. Categorization can aid interpretation but may conceal variation within categories and differences near a threshold. The registry record does not report category counts for DAS28.
What do confidence intervals and p-values add?
General: A confidence interval communicates uncertainty around an estimate under a stated statistical method. It is useful to consider the estimated effect and the interval together: the estimate describes magnitude, while the interval conveys how precisely it has been estimated. A p-value addresses compatibility between observed data and a specified null hypothesis under model assumptions; it does not measure the probability that a treatment works, nor does it measure clinical importance.
No confidence interval or p-value for the primary DAS28 endpoint is reported in the registry record. The record also does not report a detailed analysis model or a formal hypothesis for the primary outcome. It is therefore not possible to reconstruct the inferential analysis or interpret a threshold-based statistical conclusion.
What does the sample-size illustration mean?
General: A sample-size calculation is a planning exercise that estimates how many participants may be needed to detect a defined effect under specified assumptions. The registry record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are illustration assumptions, not a description of the actual single-group design.
The record does not give the numerical illustration values in the registry record for this explanation, and it does not report the trial’s own sample-size justification. A planning calculation based on an observed effect must not be treated as observed power or as evidence that the study had a particular probability of detecting an effect. The recorded enrollment of 20 is a study characteristic, not a measure of statistical power.
Why do multiplicity and over-dispersion matter in general?
General: When several outcomes or hypotheses are assessed, the chance of at least one apparently notable result can rise if each is tested without accounting for the number of tests. Statistical approaches to multiplicity can control that risk, but the appropriate method depends on the analysis plan and research question. The registry lists six outcome measures and four analyses; it does not report how those analyses were organized or whether a multiplicity adjustment was used.
General: Over-dispersion describes variability greater than a statistical model expects. It can make standard errors and confidence intervals too small if the model does not account for that extra variation. The primary outcome is described as a continuous measure summarized by a mean and standard deviation; the registry record does not report a model or an over-dispersion assessment. This concept therefore explains a general modeling concern, not a feature established for this study.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists six outcome measures and four analyses. It names DAS28 as the primary outcome and lists HAQ-DI, anti-CCP, VEGF, ESR, and CRP as secondary outcomes. However, it does not explain how the four analyses map to the six outcome measures, whether multiple time points or contrasts were tested, or which results were designated confirmatory. A multiplicity adjustment is not reported in the registry record.
General: Assessing multiple outcomes or statistical tests can increase the chance of at least one apparently unusual result under a setting where no real effects are present. Adjustments or a prespecified hierarchy can help control the interpretation of multiple tests. Without a reported analysis plan, it is not possible to determine whether such procedures were used or how they would affect interpretation.
Missing-data procedures are not reported in the registry record. The primary population is defined as all enrolled participants who received at least one dose of study treatment, but endpoint-specific numbers contributing at Day 0 and Week 24 are not reported. The record does not describe imputation, exclusion rules, or sensitivity analyses for missing measurements. The recorded enrollment of 20 should therefore not be assumed to equal the number included in every endpoint analysis.
The record does not report whether analyses followed a prespecified statistical plan, how protocol deviations were handled, or whether other analysis populations were used. These omissions limit assessment of how robust the reported conclusions would be to choices about missing observations, analysis populations, or multiple testing. No such conclusions can be recovered from the registry entry alone.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Rituximab 1000 mg | 0 | 20 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Rituximab 1000 mg | 9 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rituximab 1000 mg |
|---|---|---|
| Throat pain | Gastrointestinal disorders | 2 of 20 |
| Fever | General disorders | 2 of 20 |
| Upper respiratory tract infection | Infections and infestations | 2 of 20 |
| Mood change | Psychiatric disorders | 1 of 20 |
| Skin lesion | Skin and subcutaneous tissue disorders | 1 of 20 |
| Blood in stool | Gastrointestinal disorders | 1 of 20 |
| Cough | Respiratory, thoracic and mediastinal disorders | 1 of 20 |
| Dry eye sensation | Eye disorders | 1 of 20 |
| Blurred vision | Eye disorders | 1 of 20 |
| Feeling of weakness | General disorders | 1 of 20 |
The safety record lists 20 participants at risk for serious adverse events and zero participants affected. For other adverse events, it lists 20 at risk and nine affected. These are participant counts in the registry record; they do not indicate event severity beyond the serious-versus-other grouping or establish a causal relationship to rituximab or methotrexate. Deaths are not reported in the registry record.
General: Counts of participants affected are not interchangeable with counts of individual events. A participant may experience more than one event, but the record’s figures describe participants affected, not the total number of event episodes. A count of zero affected participants for a recorded category means no affected participants are listed for that category in this record; it does not establish that the risk is absent in other populations or settings.
The study was single-group and the safety counts have no comparator group. They therefore describe what was recorded among participants at risk in this study, but cannot quantify a comparative difference in safety. The record does not give event terms for the other adverse events or further detail on duration or severity.
12. What the Result Does, and Does Not, Mean
The registry record identifies a small, completed, open-label, single-group study of rituximab in people with active rheumatoid arthritis and an inadequate response to TNF-blocker treatment. It specifies a primary outcome, assessment times, and a primary analysis population. It also records safety counts. These details clarify what the study was designed to observe, but the registry entry does not report numerical results for the primary DAS28 outcome.
Accordingly, the record does not support a description of the average DAS28 at Day 0 or Week 24, the variation in those scores, or the numerical change between assessments. It also does not report a confidence interval or p-value for the primary outcome. The clinical categories in the DAS28 definition cannot be used to characterize the study group without its observed scores.
Even if within-group endpoint values were available, a single-group design would not show how outcomes compared with a different treatment or with no study treatment. The absence of a comparator limits causal interpretation. Open-label status and the absence of reported details about missing data, analysis methods, and multiplicity add further uncertainty about how outcomes should be interpreted.
The safety counts indicate that zero of 20 participants at risk were recorded as affected by serious adverse events, while nine of 20 were recorded as affected by other adverse events. These are descriptive observations, not comparative estimates and not proof that an event was or was not caused by study treatment. Deaths are not reported in the registry record.
General: Statistical results are most informative when the estimated magnitude, uncertainty, design, and analysis population are considered together. In this case, the record supplies design and endpoint definitions but not the primary numerical estimates or their uncertainty. The findings should therefore be understood as incompletely reported in this registry entry, rather than as evidence for a conclusion about treatment effect.
13. Why This Trial Matters Statistically
This study is statistically instructive because it makes clear that a defined endpoint and assessment schedule do not, by themselves, provide evidence about the size or precision of an outcome. The registry names DAS28, identifies Day 0 and Week 24, and specifies a mean with standard deviation. Yet without numerical results, readers cannot assess the observed scores, variation, or change over time. Transparent reporting of estimates and uncertainty is necessary for interpreting a clinical outcome.
The single-group design also illustrates why the research question must match the design. A study can describe what was observed among treated participants, but without a comparator it cannot directly estimate a treatment contrast. This distinction remains important even when an endpoint is clinically interpretable and assessed at multiple times. A before-and-after description and a comparison between treatment strategies are different statistical questions.
The record also highlights the importance of understanding the analysis population. It defines the primary population by enrollment and receipt of at least one dose, but does not report how many participants contributed endpoint measurements at each time. Enrollment alone does not establish the denominator for every analysis. Reporting endpoint-specific participant counts and the handling of missing measurements would help readers assess the analysis.
Finally, the record lists several outcome measures and analyses without describing their relationship or any multiplicity procedures. General: When many outcomes or tests are considered, a clear prespecified analysis plan helps readers distinguish primary evidence from additional exploratory findings. Here, numerical endpoint results, details of missing-data handling, and multiplicity procedures are not reported in the registry record, so those aspects of the evidence cannot be evaluated.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Several limitations arise from the information recorded for this particular study. The design is single-group, open-label, and has no listed comparator. It can describe observations among treated participants, but it cannot provide a like-for-like estimate of how outcomes would differ under another treatment strategy. Knowledge of treatment is not masked, and the record does not describe procedures for reducing possible measurement or reporting effects.
The primary endpoint is specified as mean DAS28 at Day 0 and Week 24, but its numerical results and standard deviations are not reported in the registry record. No numerical change estimate, confidence interval, or p-value is available. This prevents assessment of the observed magnitude, variability, and precision. The record also does not report endpoint-specific participant counts, so the number contributing measurements at each assessment cannot be established from the registry entry.
Although six outcome measures and four analyses are listed, the record does not describe the analysis plan, the relationship between those analyses and outcomes, or any multiplicity adjustment. Missing-data methods, sensitivity analyses, and details of other analysis populations are also not reported. The record does not provide numerical results for the listed secondary outcomes.
Safety reporting is limited to participant counts for serious and other adverse events; deaths are not reported in the registry record. Event terms for the other adverse events and comparative safety data are not given. These limits mean that the counts cannot support a detailed characterization of event types or a controlled comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Had an Inadequate Response to a TNF-Blocker. — NCT00424502.
- Registry record last updated 2016-05-09; status last verified 2016-04.
- Results first posted 2014-07-14.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
This completed Phase 4 study enrolled 20 participants with rheumatoid arthritis who had an inadequate response to one or more TNF blockers. It was open-label and single-group, with no separate comparator listed. The study summary describes rituximab 1 g infusions on Day 1 and Day 15 alongside continued methotrexate at 10–25 mg per week.
The primary outcome was mean DAS28, assessed at Day 0 and Week 24, among enrolled participants who received at least one dose. Numerical primary outcome results are not reported in the registry record. The record lists HAQ-DI, anti-CCP, VEGF, ESR, and CRP among the secondary outcomes.
The safety record lists zero participants affected by serious adverse events among 20 at risk and nine affected by other adverse events among 20 at risk. Deaths are not reported in the registry record. The absence of a comparator and of numerical primary endpoint results limits interpretation of treatment effects and endpoint precision.